{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:30:24Z","timestamp":1790674224714,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2010,4,8]],"date-time":"2010-04-08T00:00:00Z","timestamp":1270684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2010,4,8]],"date-time":"2010-04-08T00:00:00Z","timestamp":1270684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gene Ther"],"published-print":{"date-parts":[[2010,6]]},"DOI":"10.1038\/gt.2010.41","type":"journal-article","created":{"date-parts":[[2010,4,8]],"date-time":"2010-04-08T06:26:33Z","timestamp":1270707993000},"page":"790-798","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["PPAR\u03b3 is essential for protection against nonalcoholic steatohepatitis"],"prefix":"10.1038","volume":"17","author":[{"given":"C W","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E S H","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C N Y","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A S L","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C W","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V W S","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J Y","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,4,8]]},"reference":[{"key":"BFgt201041_CR1","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1210\/endo.135.2.8033830","volume":"135","author":"A Chawla","year":"1994","unstructured":"Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA . Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 1994; 135: 798\u2013800.","journal-title":"Endocrinology"},{"key":"BFgt201041_CR2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2174\/157339907779802067","volume":"3","author":"MA Jay","year":"2007","unstructured":"Jay MA, Ren J . Peroxisome proliferator-activated receptor (PPAR) in metabolic syndrome and type 2 diabetes mellitus. Curr Diabetes Rev 2007; 3: 33\u201339.","journal-title":"Curr Diabetes Rev"},{"key":"BFgt201041_CR3","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1056\/NEJMoa060326","volume":"355","author":"R Belfort","year":"2006","unstructured":"Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297\u20132307.","journal-title":"N Engl J Med"},{"key":"BFgt201041_CR4","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/hep.21661","volume":"46","author":"G Lutchman","year":"2007","unstructured":"Lutchman G, Modi A, Kleiner DE, Promrat K, Heller T, Ghany M et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 2007; 46: 424\u2013429.","journal-title":"Hepatology"},{"key":"BFgt201041_CR5","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/hep.21881","volume":"46","author":"SH Caldwell","year":"2007","unstructured":"Caldwell SH, Argo CK . Divergent effects of peroxisome proliferator-activated receptor-gamma ligands in human and mouse nonalcoholic steatohepatitis. Hepatology 2007; 46: 285\u2013287.","journal-title":"Hepatology"},{"key":"BFgt201041_CR6","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1002\/hep.21108","volume":"43","author":"J Yu","year":"2006","unstructured":"Yu J, Ip E, Dela Pena A, Hou JY, Sesha J, Pera N et al. COX-2 induction in mice with experimental nutritional steatohepatitis: role as pro-inflammatory mediator. Hepatology 2006; 43: 826\u2013836.","journal-title":"Hepatology"},{"key":"BFgt201041_CR7","unstructured":"The Jackson Laboratory. Technical document 006142. Available at http:\/\/jaxmice.jax.org\/strain\/006142.htmlAccessed April 2008."},{"key":"BFgt201041_CR8","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1172\/JCI1235","volume":"101","author":"A Okuno","year":"1998","unstructured":"Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 1998; 101: 1354\u20131361.","journal-title":"J Clin Invest"},{"key":"BFgt201041_CR9","doi-asserted-by":"publisher","first-page":"41245","DOI":"10.1074\/jbc.M103241200","volume":"276","author":"T Yamauchi","year":"2001","unstructured":"Yamauchi T, Kamon J, Waki H, Murakami K, Motojima K, Komeda K et al. The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 2001; 276: 41245\u201341254.","journal-title":"J Biol Chem"},{"key":"BFgt201041_CR10","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1002\/hep.21687","volume":"46","author":"I Garc\u00eda-Ruiz","year":"2007","unstructured":"Garc\u00eda-Ruiz I, Rodr\u00edguez-Juan C, D\u00edaz-Sanju\u00e1n T, Mart\u00ednez MA, Mu\u00f1oz-Yag\u00fce T, Sol\u00eds-Herruzo JA . Effects of rosiglitazone on the liver histology and mitochondrial function in ob\/ob mice. Hepatology 2007; 46: 414\u2013423.","journal-title":"Hepatology"},{"key":"BFgt201041_CR11","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1074\/jbc.M210062200","volume":"278","author":"S Yu","year":"2003","unstructured":"Yu S, Matsusue K, Kashireddy P, Cao WQ, Yeldandi V, Yeldandi AV et al. Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (PPARgamma1) overexpression. J Biol Chem 2003; 278: 498\u2013505.","journal-title":"J Biol Chem"},{"key":"BFgt201041_CR12","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nm1025","volume":"10","author":"RM Evans","year":"2004","unstructured":"Evans RM, Barish GD, Wang YX . PPARs and the complex journey to obesity. Nat Med 2004; 10: 355\u2013361.","journal-title":"Nat Med"},{"key":"BFgt201041_CR13","first-page":"73","volume":"58","author":"A Chabowski","year":"2007","unstructured":"Chabowski A, Zmijewska M, Gorski J, Bonen A, Kami\u00f1ski K, Winnicka MM . Effect of IL-6 deficiency on myocardial expression of fatty acid transporters and intracellular lipid deposits.J Physiol Pharmacol 2007; 58: 73\u201382.","journal-title":"J Physiol Pharmacol"},{"key":"BFgt201041_CR14","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.beem.2005.07.005","volume":"19","author":"H Al-Hasani","year":"2005","unstructured":"Al-Hasani H, Joost HG . Nutrition-\/diet-induced changes in gene expression in white adipose tissue. Best Pract Res Clin Endocrinol Metab 2005; 19: 589\u2013603.","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"BFgt201041_CR15","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1056\/NEJMra041001","volume":"351","author":"H Yki-Jarvinen","year":"2004","unstructured":"Yki-Jarvinen H . Thiazolidinediones. N Engl J Med 2004; 351: 1106\u20131118.","journal-title":"N Engl J Med"},{"key":"BFgt201041_CR16","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1002\/hep.20170","volume":"39","author":"E Ip","year":"2004","unstructured":"Ip E, Farrell G, Hall P, Robertson G, Leclercq I . Administration of the potent PPARalpha agonist, Wy-14\u2009643, reverses nutritional fibrosis and steatohepatitis in mice. Hepatology 2004; 39: 1286\u20131296.","journal-title":"Hepatology"},{"key":"BFgt201041_CR17","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1172\/JCI200317797","volume":"112","author":"A Xu","year":"2003","unstructured":"Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ . The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91\u2013100.","journal-title":"J Clin Invest"},{"key":"BFgt201041_CR18","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1056\/NEJM200011163432007","volume":"343","author":"H Tilg","year":"2000","unstructured":"Tilg H, Diehl AM . Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000; 343: 1467\u20131476.","journal-title":"N Engl J Med"},{"key":"BFgt201041_CR19","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1053\/jhep.2003.50316","volume":"38","author":"M Kugelmas","year":"2003","unstructured":"Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ . Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 2003; 38: 413\u2013419.","journal-title":"Hepatology"},{"key":"BFgt201041_CR20","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1038\/ncprheum0674","volume":"3","author":"F Lago","year":"2007","unstructured":"Lago F, Dieguez C, Gomez-Reino J, Gualillo O . Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 2007; 3: 716\u2013724.","journal-title":"Nat Clin Pract Rheumatol"},{"key":"BFgt201041_CR21","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1016\/j.cgh.2006.06.011","volume":"4","author":"VW Wong","year":"2006","unstructured":"Wong VW, Hui AY, Tsang SW, Chan JL, Tse AM, Chan KF . Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006; 4: 1154\u20131161.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"BFgt201041_CR22","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1210\/er.2005-0005","volume":"26","author":"T Kadowaki","year":"2005","unstructured":"Kadowaki T, Yamauchi T . Adiponectin and adiponectin receptors. Endocr Rev 2005; 26: 439\u2013451.","journal-title":"Endocr Rev"},{"key":"BFgt201041_CR23","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1001\/jama.286.3.327","volume":"286","author":"AD Pradhan","year":"2001","unstructured":"Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM . C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: 327\u2013334.","journal-title":"JAMA"},{"key":"BFgt201041_CR24","doi-asserted-by":"publisher","first-page":"3391","DOI":"10.2337\/diabetes.51.12.3391","volume":"51","author":"JJ Senn","year":"2002","unstructured":"Senn JJ, Klover PJ, Nowak IA, Mooney RA . Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 2002; 51: 3391\u20133399.","journal-title":"Diabetes"},{"key":"BFgt201041_CR25","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/nrm2391","volume":"9","author":"A Guilherme","year":"2008","unstructured":"Guilherme A, Virbasius JV, Puri V, Czech MP . Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 367\u2013377.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFgt201041_CR26","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/0026-0495(87)90044-8","volume":"36","author":"JH Henriksen","year":"1987","unstructured":"Henriksen JH, Tronier B, Bulow JB . Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man. Metabolism 1987; 36: 463\u2013468.","journal-title":"Metabolism"},{"key":"BFgt201041_CR27","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1046\/j.1440-1746.2003.02989.x","volume":"18","author":"GC Farrell","year":"2003","unstructured":"Farrell GC . Non-alcoholic steatohepatitis: what is it, and why is it important in the Asia-Pacific region? J Gastroenterol Hepatol 2003; 18: 124\u2013138.","journal-title":"J Gastroenterol Hepatol"},{"key":"BFgt201041_CR28","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1002\/hep.22039","volume":"47","author":"B Shen","year":"2008","unstructured":"Shen B, Yu J, Wang S, Chu ES, Wong VW, Zhou X et al. Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo. Hepatology 2008; 47: 473\u2013483.","journal-title":"Hepatology"},{"key":"BFgt201041_CR29","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/34184","volume":"391","author":"C Jiang","year":"1998","unstructured":"Jiang C, Ting AT, Seed B . PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998; 391: 82\u201386.","journal-title":"Nature"},{"key":"BFgt201041_CR30","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1038\/nm780","volume":"8","author":"HP Guan","year":"2002","unstructured":"Guan HP, Li Y, Jensen MV, Newgard CB, Steppan CM, Lazar MA . A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat Med 2002; 8: 1122\u20131128.","journal-title":"Nat Med"},{"key":"BFgt201041_CR31","doi-asserted-by":"publisher","first-page":"2607","DOI":"10.1128\/MCB.22.8.2607-2619.2002","volume":"22","author":"TE Akiyama","year":"2002","unstructured":"Akiyama TE, Sakai S, Lambert G, Nicol CJ, Matsusue K, Pimprale S et al. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol Cell Biol 2002; 22: 2607\u20132619.","journal-title":"Mol Cell Biol"},{"key":"BFgt201041_CR32","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1093\/carcin\/bgh160","volume":"25","author":"CJ Nicol","year":"2004","unstructured":"Nicol CJ, Yoon M, Ward JM, Yamashita M, Fukamachi K, Peters JM et al. PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis 2004; 25: 1747\u20131755.","journal-title":"Carcinogenesis"}],"updated-by":[{"DOI":"10.1038\/s41434-025-00568-z","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000}}],"container-title":["Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/gt201041.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gt201041","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gt201041.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T14:32:12Z","timestamp":1758897132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/gt201041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,8]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,6]]}},"alternative-id":["BFgt201041"],"URL":"https:\/\/doi.org\/10.1038\/gt.2010.41","relation":{},"ISSN":["0969-7128","1476-5462"],"issn-type":[{"value":"0969-7128","type":"print"},{"value":"1476-5462","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,8]]},"assertion":[{"value":"7 September 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2009","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2009","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2010","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2025","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41434-025-00568-z","URL":"https:\/\/doi.org\/10.1038\/s41434-025-00568-z","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}